Previous studies in our laboratory have shown that the tumor-bearing host can mount a cell-mediated reactivity against its neoplasm (capable of destroying the tumor cells in vitro) and that the effectiveness of this reactivity is generally blocked by serum factors, which are most likely complexes between antigens released from the tumor and antibodies formed by the host. Certain leads for tumor therapy have been suggested by these findings, mosts notably the employment of "unblocking" antibodies, capable of cancelling the ability of the blocking factors to inhibit cell-mediated reactivity. A situation somewhat similar to that seen in tumor-bearing animals has been encountered in animals made neonatally tolerant to skin grafts, as defined by their ability to permanently accept such. Our present work concerns an exploration of the cell types involved in the immune defense to the tumor antigens, in animals and in man, of the molecules blocking the immune response, of the interaction between the effector cells, the blocking factors and the target cells, both in tumor immunity and in allograft for immunoprophylaxis and immunotherapy of tumors, such as chemically induced bladder carcinomas of mice and rats, which have a common, tissue type specific tumor antigen.